Probing Selenium-Deficient\nChicken Spleen Th1/Th17\nDifferentiation Based on Selenoprotein W Targeting of PKM2/HIF1α

Selenium regulates the differentiation and function of\nimmune cells\nmainly through selenoproteins. Selenoprotein W (SelW) has been shown\nto mitigate inflammatory bowel disease in mice by modulating the differentiation\nof helper T (CD4<sup>+</sup> T) cell. Previous studies by our team\nhave underscored SelW’s critical role in safeguarding chicken\nspleens and splenic lymphocytes against inflammatory injury. However,\nresearch examining SelW’s involvement in regulating CD4<sup>+</sup> T cell differentiation in avian spleens remains scarce. Therefore,\nthe selenium-deficient chicken model was constructed in this study.\nIt was found that the spleen of selenium-deficient chickens showed\nsignificant inflammatory damage, accompanied by decreased SelW expression,\ndiminished antioxidant capacity, heightened glycolysis, and an elevated\ncount of Th1/Th17 cells. To elucidate the specific mechanism of SelW\nregulating Th1/Th17 cell differentiation, this study used molecular\ndocking technology, fluorescence colocalization, and co-immunoprecipitation\nand initially confirmed the targeting relationship between SelW and\npyruvate kinase M2 (PKM2). Subsequently, an <i>in vitro</i> model of SelW overexpression, knockdown, and TEPP-46 (PKM2 tetramer\nactivator) cotreatment of chicken primary splenic lymphocytes was\nreplicated. Our findings revealed that selenium deficiency triggers\noxidative stress and promotes PKM2 nuclear translocation via SelW\ndownregulation, which stabilizes HIF1α transcription in the\nnucleus, enhancing glycolysis and skewing chicken splenic CD4<sup>+</sup> T cells toward the Th1/Th17 phenotype. Our study, for the\nfirst time, demonstrates the existence of an interaction between SelW\nand PKM2 in poultry, emphasizing SelW’s paramount significance\nin CD4<sup>+</sup> T cell differentiation, providing fresh perspectives\non the contributions of selenoproteins to T cell biology and immune\nprocesses.